Effect of ranolazine on ventricular vulnerability and defibrillation threshold in the intact porcine heart

Introduction: Extensive in vitro studies and clinical evidence (MERLIN trial) indicate an antiarrhythmic potential of ranolazine, a novel antianginal agent. Programmed electrophysiologic testing was performed to quantify ranolazine's effects on ventricular vulnerability and defibrillation thresholds and to gain insights into mechanisms. Methods and Results: Effects of ranolazine (9.2 ± 2.1 μM, plasma level) on surface ECG, right ventricular effective refractory period (ERP), and repetitive extrasystole (RE), ventricular fibrillation (VF), and defibrillation (DFT) thresholds were determined in 29 normal closed‐chest anesthetized pigs. The single extrastimulus method was employed for ERP and for RE and VF thresholds. DFT₅₀ was determined using an up‐down testing protocol with an implantable cardioverter‐defibrillator. Ranolazine increased rate‐corrected QT interval from 490 ± 30 to 527 ± 24 ms (P < 0.05) but did not alter T_peak‐T_end interval (59 ± 8 to 62 ± 11, P = 0.65). ERP increased by 40 ± 6 ms (P < 0.001). Compared with baseline, ranolazine raised RE threshold from 20 ± 6 to 34 ± 9 mA (P < 0.001) and VF threshold from 38 ± 4 to 48 ± 10 mA (P < 0.05). DFT₅₀ was unchanged (baseline: 14 ± 2 J; ranolazine: 14 ± 2 J; P = 0.6), whereas diastolic pacing threshold increased from baseline pulse width of 0.07 ± 0.03 to 0.17 ± 0.07 ms (P < 0.01) with 1V pulse amplitude. Conclusions: Ranolazine, at therapeutic concentrations, produces a mild increase in QT interval and a marked increase in both RE and VF thresholds. Thus, ranolazine does not augment and may improve dispersion of ventricular repolarization, suggesting a potential antiarrhythmic action. Ranolazine is unlikely to affect the margin of safety of defibrillation, given no significant effect on DFT, but could result in a mild increase in pacing threshold.     

Determinant of factors associated with child health outcomes and service utilization in Ghana: multiple indicator cluster survey conducted in 2011

Background

The effects of National Health Insurance Scheme in Ghana and its impact on child health outcome and service utilization cannot be underestimated. Despite the tremendous improvement in child health care in Ghana, there are still some challenges in relation to how National health insurance membership, socioeconomic status and other demographic factors impacts on child health outcomes. The study seeks to determine the association between NHIS membership, socio-economic status, geographic location and other relevant background factors, on child health service utilization and outcomes.

Methods

Secondary data from the Multiple Indicator Cluster Survey conducted in 2011 was used. Multivariate analysis based on Binary Logistic Regression Models and Multiple linear regression techniques was applied to determine factors associated with child health outcomes and service utilization. Collection of best models was based on Hosmer-Lemeshow Goodness-Of-Fit as one criterion of fit and the Akaike Information Criterion.

Results

Controlling for confounding effect of socioeconomic status, age of the child, mothers education level and geographic location, the odds of a child developing anemia for children with National Health Insurance Scheme Membership is 65.2% [95% CI: 52.9-80.2] times less than children without National Health Insurance Scheme Membership. The odds of being fully immunized against common childhood illnesses for children with NHIS membership is 2.3[95% CI: 1.4-3.7] times higher than children without National Health Insurance Scheme Membership. There was no association between National Health Insurance Scheme Membership and stunted growth in children.

Conclusions

National Health Insurance Scheme Membership was found to be related to child health service utilization (full immunization) of children under five a child’s anemia status. Children with NHIS are more likely to be fully immunized against common childhood diseases and are less likely to develop anemia. Stunted growth of children was not associated with National Health Insurance Scheme Membership. Health Education on the registration and the use of the National Health Insurance should be made a national priority to enable the Ministry of Health achieve routine Immunization targets and to reduce to the bearers minimum prevalence of anemia.

     

Processing of a cowpea–groundnut blend into a miso-like product

A traditional salt-miso process was used to produce a miso-like product from a 50–50 mixture of cowpea and groundnuts in a 60-day fermentation process as part of a study to determine the suitability of local legumes as raw materials for the production of miso. The koji was freshly prepared from a locally obtained rice and Aspergillus oryzae spores obtained from Japan. An old miso sample also obtained from Japan was used as the source of lactic acid bacteria. The physico-chemical changes in the product associated with the fermentation and the functional and quality characteristics of the final product were determined. The study demonstrated the possibility of processing the legume blend into a miso-like product. The physico-chemical, functional and quality characteristics of the final product showed the suitability of the product for its intended use as a soup base. The product had a high protein and a moderately high lipid content (about 25% and 29%, respectively), which could contribute to the nutritional contents of diets.     

In vitro activity of extract and fractions of natural cocoa powder on Plasmodium falciparum

Several flavonoids isolated from certain plants have demonstrated antiplasmodial activity, after their initial indigenous use in malaria treatment. Cocoa has been found to be a rich food source of flavonoids in comparison with many common foods and beverages. The aim of this work was to investigate the in vitro activity of natural cocoa powder on the growth of Plasmodium falciparum. Prepared crude methanol extract was partitioned successively with petroleum ether, ethyl acetate, chloroform, and butanol. Total flavonoid concentration in the crude methanol extract and fractions was measured by the AlCl(3) colorimetric assay. Direct inhibitory activity of the natural cocoa powder was assessed by culturing extract and fractions with P. falciparum in vitro. Greater antiplasmodial activity was observed in nonpolar solvent fractions (chloroform, ethyl acetate, and petroleum ether) compared with polar solvents. The chloroform fraction was most active, with mean±SEM 50% and 90% inhibition concentrations of 48.3±0.9 and 417±7.8 μg/mL, respectively. The study showed a weak association between total flavonoid concentration and antiplasmodial activity. Early trophozoite (ring-stage) synchronized cultures treated with the chloroform fraction of natural cocoa powder showed a decline in growth. Further reduction in parasitemia was also observed for other erythrocytic stages. These results suggest that natural cocoa powder has measurable direct in vitro inhibitory effect on P. falciparum and support the anecdotal reports of its ability to prevent malaria as a result of regular intake as a beverage.     

Atrioventricular nodal reentrant tachycardia in two siblings with Wolfram syndrome

This is a case of two siblings with the autosomal recessive Wolfram syndrome who both have documented atrioventricular nodal reentrant tachycardia (AVNRT). This is the first report to our knowledge that links AVNRT to a syndrome in which the putative gene has been identified.     

Marijuana use and suicidal behaviours among school-going adolescents in Africa: assessments of prevalence and risk factors from the Global School-Based Student Health Survey

BackgroundMarijuana use among adolescents, including high school students, has been consistently reported to be associated with a high incidence of suicidal behaviours. Little empirical research has been conducted on the propensity impact of marijuana use on suicidal behaviours in Africa.AimsTo assess factors associated with marijuana use and further quantify marijuana use as an associated factor of suicidal behaviours, including repeated attempted suicide, suicidal ideation and suicide planning, among high school students in Africa.MethodsA cross-sectional study was conducted among 32 802 school-going adolescents using the Global School-Based Student Health Survey data from 10 African countries grouped into West Africa, North Africa, South-East Africa, South Africa and East Africa subregions. Marijuana use and repeated attempted suicide were the main outcome variables. We employed double selection least absolute shrinkage and selection operator poisson regression model to assess risk factors associated with marijuana use and dominance analysis to establish ranked important and common risk factors. Inverse probability weighting poisson regression adjustment was applied to assess impact.ResultsThe prevalence of marijuana use and repeated attempted suicide were 3.7% (95% CI: 3.1 to 4.3) and 6.6% (95% CI: 5.9 to 7.4), respectively. The most important risk factor for marijuana use generally across the countries and specifically in three subregions was alcohol consumption, which constituted approximately 40% of the impact. The average treatment effect on the treated (ATT) indicated that marijuana use significantly increased the risk of suicidal ideation, suicide planning and repeated attempted suicide by 12% (ATT=0.12 (95% CI: 0.02 to 0.22)), 18% (ATT=0.18 (95% CI: 0.13 to 0.22)) and 31% (ATT=0.31 (95% CI: 0.20 to 0.41)), respectively.ConclusionsMarijuana use was significantly associated with suicidal behaviours (suicidal ideation, planning and repeated attempted suicide) among the students. To achieve Sustainable Development Goal 3.5 (to strengthen prevention and treatment of substance abuse), school-based psychosocial interventions should be streamlined to adequately assess and manage marijuana use. Targeting the most dominant risk factors in this population could translate into the reduction of suicidal behaviours in countries within Africa.     

High risk of vitamin D deficiency in children with sickle cell disease

Vitamin D is a particularly concerning nutrient for children with homozygous SS sickle cell disease (SCD-SS) due to their increased skin melanin concentrations, reduced levels of physical activity, and poor vitamin D intake. The goal of this study was to compare the vitamin D status of children with SCD-SS to healthy African-American children living in the same geographic area. Growth, dietary intake, serum 25-hydroxyvitamin D [25(OH)D], and intact parathyroid hormone (iPTH) concentrations were measured in 61 African-American subjects with SCD-SS and 89 healthy African-American control subjects age 5 to 18 years from the Philadelphia, PA, region (latitude 39.95 degrees N). Median serum 25(OH)D concentrations were 15 ng/mL (95% confidence interval [CI]: 13, 17) in subjects with SCD-SS and 21 ng/mL (95% CI: 18, 22) in healthy control subjects (P<0.0002). Vitamin D deficiency [25(OH)D<11 mg/mL] was found in 33% of subjects with SCD-SS and 9% of healthy control subjects (P<0.001); 25% of subjects with SCD-SS and 17% of healthy control subjects had elevated iPTH [(>59 rhog/mL), P<0.05]. Ninety-three percent of subjects with SCD-SS and 90% of healthy subjects had vitamin D insufficiency [25(OH)D<30 mg/mL]. The risk of vitamin D deficiency among subjects with SCD-SS was 5.3 (95% CI: 2.5, 8.2) times greater than control subjects, adjusted for season and age. Poor vitamin D status was prevalent in children with SCD-SS and healthy African-American children living in the same geographic area. However, children with SCD-SS were at greater risk for vitamin D deficiency than healthy African-American children.